Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension.
Sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO; Et2N-[N(O)NO]Na) is a compound that spontaneously generates nitric oxide (NO). Because of its short half-life (2.1 min), we hypothesized that inhaling DEA/NO aerosol would selectively dilate the pulmonary circulation without decreasing systemic arterial pressure. We compared the pulmonary selectivity of this new NO donor with two other reference drugs: inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheep with pulmonary hypertension induced by the infusion of U-46619, we compared the hemodynamic effects of DEA/NO with those of incremental doses of inhaled NO gas. In seven additional awake sheep, we examined the hemodynamic effects of incremental doses of inhaled nitroprusside (i.e., SNP). Inhaled NO gas selectively dilated the pulmonary vasculature. Inhaled DEA/NO produced nonselective vasodilation; both systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were reduced. Inhaled SNP selectively dilated the pulmonary circulation at low concentrations (< or = 10(-2)M), inducing a decrease of PVR of up to 42% without any significant decrease of SVR(-5%), but nonselectively dilated the systemic circulation at larger doses (> 10(-2)M). In conclusion, despite its short half-life, DEA/NO is not a selective pulmonary vasodilator compared with inhaled NO. Inhaled SNP appears to be selective to the pulmonary circulation at low doses but not at higher levels.
Adrie
C
C
Department of Anesthesia and Critical Care, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Ichinose
F
F
Holzmann
A
A
Keefer
L
L
Hurford
W E
WE
Zapol
W M
WM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology / Q000633:toxicity; D000208:Acute Disease; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006834:Hydrazines / Q000008:administration & dosage / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D009589:Nitrogen Oxides; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D011355:Prodrugs / Q000008:administration & dosage / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D014662:Vasoconstrictor Agents / Q000633:toxicity; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000336:Aerosols; D006834:Hydrazines; D009589:Nitrogen Oxides; D011355:Prodrugs; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine